Abstract

A regular menstrual cycle is a sign of a normally functioning pituitary–ovarian axis and is thus often interpreted as a sign of good reproductive and general health. In a recent study, menstrual cycles proved to be ovulatory in 96% of women reporting regular cycles (1). However, from the reproductive point of view, each menstrual period can also be viewed as a sign of reproductive failure and a side effect of the present-day high standard of living. A modern day woman may experience up to 450 menstrual periods in her lifetime, whereas the number of menstrual bleeds for our ancestors has been calculated to be approximately 50–150, interspaced by pregnancies, prolonged periods of lactation and amenorrhea (2). When combined oral contraceptives (COCs) were developed during the late 1950s, three weeks of hormone administration were interspaced with a pill-free week, resulting in regular withdrawal bleeding. Thus COCs could be marketed as ‘natural family planning’ (3). However, regular uterine bleeding is associated with no known health benefit (2). In addition, the negative symptoms associated with the use of COCs – pelvic pain, headache, bloating or swelling, and breast tenderness – are most prevalent during the pill-free week (4). Would it therefore be time to move forward? The necessity of monthly menstruation is viewed differently in different cultures. In a telephone survey performed among Dutch women, 21–38% of the women indicated that menstruation every 3 months would be preferable and 22–25% would prefer never to bleed (5). As judged by the common use of the levonorgestrel-releasing intrauterine system, and resulting oligo/amenorrhea (6), the presumed importance of regular uterine bleeding is rapidly diminishing in the Nordic countries. Strategies to reduce regular bleeding by means of COCs are also emerging. A COC containing 30 μg of ethinylestradiol and 150 μg of levonorgestrel, specially designed for extended cycles, with 84 successive active tablets (Seasonale®), was introduced to the North American market in 2003 (7). However, any available monophasic COC can be used in an extended fashion. Besides oral preparations, the recently introduced contraceptive vaginal ring and contraceptive patch may also be used in an extended fashion (8, 9). In studies in which extended versus conventional use of COCs has been evaluated, significantly less bleeding and fewer negative side effects have been observed among women randomized to extended cycles (10, 11). The proportion of women completing the reported one-year trials has been similar among those randomized to extended or to conventional use of COCs (7, 10, 11). An extended cycle requires more tablets, but the increased cost is compensated for by a reduced need of sanitary products (10). In a recent study in which extended use of a contraceptive vaginal ring was evaluated, user satisfaction was greatest in the group randomized to six weeks of continuous use of the ring (8). Poor compliance has been pointed out as the main reason for oral contraceptive failure (12). In Finland ∼10% of women requesting termination of early pregnancy report having used oral contraceptives at the time of conception (http://www.stakes.fi). Extended cycle regimens offer fewer chances for unintended extension of the pill-free interval. Thus an important aim motivating the development of extended cycle combined contraception is to increase compliance in contraceptive use. In the single randomized study in which contraceptive efficacy was evaluated, the Pearl Index was comparable in the groups randomized to extended or conventional use of COCs (7). Long-cycle contraceptive strategies are especially valuable when caring for women with menstrual complaints. Sulak et al. (13) investigated extended use of COCs among women suffering from debilitating pelvic pain, headache, heavy bleeding, or premenstrual-type symptoms during the pill-free week. A majority (74%) of the 50 women studied showed improvement on extended cycle regimens of 6–12 weeks of active pill use (13). Endometriosis-associated dysmenorrhea, which persisted despite conventional use of COCs, has been reported to be significantly alleviated during continuous use (14). Extended cycles mean increased use of exogenous steroids – are there thus safety concerns? In the studies reported, the results of various safety tests have remained normal. In histology, the endometrium was either inactive or atrophic in the majority of women during continuous use of COCs containing ethinylestradiol and levonorgestrel (11). Deep venous thromboembolism (DVT) has been described in two women randomized to extended cycle regimens (7, 8). However, given the rarity of DVT, no conclusions can be drawn from individual cases. Potential adverse effects will be closely monitored as specific preparations designed for extended cycles are introduced to the contraceptive market. In conclusion, extended cycle contraceptive regimens are especially valuable when caring for women with complicated menstrual periods. Use of such regimens can also be suggested to all women wishing to reduce uterine bleeding. It is hoped that increased flexibility will improve compliance and eventually also decrease the number of unplanned pregnancies. Oskari Heikinheimo

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